德国海德堡干细胞技术和实验医学研究所Simon Haas等研究人员合作发现，抗原呈递保障造血干细胞库的完整性。该项研究成果发表在2022年5月5日出版的《细胞—干细胞》杂志上。

研究人员发现，造血干细胞和祖细胞（HSPC）通过主要组织相容性复合体II类组成性地呈递抗原。在恶性转化过程中出现的免疫原性抗原的呈递引发了HSPC和抗原特异性CD4⁺T细胞之间的双向互动，导致干细胞增殖、分化和异常HSPC的特异性耗竭。这种免疫监视机制有效地从造血系统中消除了转化的HSPC，从而防止了白血病的发生。这些数据共同揭示了HSPC和CD4⁺T细胞之间的双向互动，表明HSPC不仅是免疫信号的被动接受者，而且还积极参与适应性免疫反应，从而保障干细胞库的完整性。

据悉，HSPC负责生产血液和免疫细胞。在整个生命过程中，HSPC会获得致癌畸变，从而导致血液学癌症。虽然维持干细胞完整性的分子程序已被确定，但从干细胞池中消除恶性HSPC的安全机制仍然没有得到很好的描述。

附：英文原文

Title: Antigen presentation safeguards the integrity of the hematopoietic stem cell pool

Author: Pablo Hernández-Malmierca, Dominik Vonficht, Alexandra Schnell, Hannah J. Uckelmann, Alina Bollhagen, Mohamed A.A. Mahmoud, Sophie-Luise Landua, Elise van der Salm, Christine L. Trautmann, Simon Raffel, Florian Grünschlger, Raphael Lutz, Michael Ghosh, Simon Renders, Nádia Correia, Elisa Donato, Karin O. Dixon, Christoph Hirche, Carolin Andresen, Claudia Robens, Paula S. Werner, Tobias Boch, David Eisel, Wolfram Osen, Franziska Pilz, Adriana Przybylla, Corinna Klein, Frank Buchholz, Michael D. Milsom, Marieke A.G. Essers, Stefan B. Eichmüller, Wolf-Karsten Hofmann, Daniel Nowak, Daniel Hübschmann, Michael Hundemer, Christian Thiede, Lars Bullinger, Carsten Müller-Tidow, Scott A. Armstrong, Andreas Trumpp, Vijay K. Kuchroo, Simon Haas

Issue&Volume: 2022/05/05

Abstract: Hematopoietic stem and progenitor cells (HSPCs) are responsible for the productionof blood and immune cells. Throughout life, HSPCs acquire oncogenic aberrations thatcan cause hematological cancers. Although molecular programs maintaining stem cellintegrity have been identified, safety mechanisms eliminating malignant HSPCs fromthe stem cell pool remain poorly characterized. Here, we show that HSPCs constitutivelypresent antigens via major histocompatibility complex class II. The presentation ofimmunogenic antigens, as occurring during malignant transformation, triggers bidirectionalinteractions between HSPCs and antigen-specific CD4+ T cells, causing stem cell proliferation, differentiation, and specific exhaustionof aberrant HSPCs. This immunosurveillance mechanism effectively eliminates transformedHSPCs from the hematopoietic system, thereby preventing leukemia onset. Together,our data reveal a bidirectional interaction between HSPCs and CD4+ T cells, demonstrating that HSPCs are not only passive receivers of immunologicalsignals but also actively engage in adaptive immune responses to safeguard the integrityof the stem cell pool.

DOI: 10.1016/j.stem.2022.04.007

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00160-6